Journal article
HIV-1 is dependent on its immature lattice to recruit IP6 for mature capsid assembly
Nature structural & molecular biology, Vol.30(3), pp.370-382
03/2023
DOI: 10.1038/s41594-022-00887-4
PMCID: PMC7614341
PMID: 36624347
Abstract
HIV-1 Gag metamorphoses inside each virion, from an immature lattice that forms during viral production to a mature capsid that drives infection. Here we show that the immature lattice is required to concentrate the cellular metabolite inositol hexakisphosphate (IP6) into virions to catalyze mature capsid assembly. Disabling the ability of HIV-1 to enrich IP6 does not prevent immature lattice formation or production of the virus. However, without sufficient IP6 molecules inside each virion, HIV-1 can no longer build a stable capsid and fails to become infectious. IP6 cannot be replaced by other inositol phosphate (IP) molecules, as substitution with other IPs profoundly slows mature assembly kinetics and results in virions with gross morphological defects. Our results demonstrate that while HIV-1 can become independent of IP6 for immature assembly, it remains dependent upon the metabolite for mature capsid formation.
Details
- Title: Subtitle
- HIV-1 is dependent on its immature lattice to recruit IP6 for mature capsid assembly
- Creators
- Nadine Renner - MRC Laboratory of Molecular BiologyAlex Kleinpeter - Center for Cancer ResearchDonna L. Mallery - MRC Laboratory of Molecular BiologyAnna Albecka - MRC Laboratory of Molecular BiologyRifat K. M. Faysal - UNSW SydneyTill Bocking - UNSW SydneyAdolfo Saiardi - University College LondonEric O. Freed - Center for Cancer ResearchLeo C. James - MRC Laboratory of Molecular Biology
- Resource Type
- Journal article
- Publication Details
- Nature structural & molecular biology, Vol.30(3), pp.370-382
- DOI
- 10.1038/s41594-022-00887-4
- PMID
- 36624347
- PMCID
- PMC7614341
- NLM abbreviation
- Nat Struct Mol Biol
- ISSN
- 1545-9993
- eISSN
- 1545-9985
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 30
- Grant note
- Intramural AIDS Research Fellowship 200594/Z/16/Z; 214344/A/18/Z / Wellcome Trust Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 200594/Z/16/Z / Wellcome Trust Investigator Award; Wellcome Trust 214344/A/18/Z / Wellcome Trust Collaborator Award; Wellcome Trust MR/T028904/1 / MRC UK; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) U105181010 / Medical Research Council (MRC UK); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MR/T028904/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) APP1182212 / NHMRC; National Health & Medical Research Council (NHMRC) of Australia
- Language
- English
- Date published
- 03/2023
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984827337802771
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